The ability to respond to stress is an important basic adaptive mechanism. Hyper-responsiveness or a deficit in the capacity to adapt to adapt to or recover from stress could ultimately affect an organism's health, in that prolonged stress levels of glucocorticoids are associated with sustained alterations in metabolism and immunosuppression. The present research will systematically document changes in stress responsiveness induced by ethanol exposure, either in utero or in adulthood, and will investigate one possible mechanism which may mediate these changes. The following hypotheses will be tested: 1) sex differences in stress responsiveness consistently occur following prenatal ethanol exposure; 2) the impaired capacity of fetal ethanol- exposed animals to adapt to and recover from stress is a robust and generalized phenomenon; 3) chronic ethanol intake in adulthood increases stress responsiveness and produces deficits in adaptation to or recovery from stress; 4) chronic ethanol consumption may differentially affect adult males and females; 5) a decrease in hippocampal glucocorticoid receptor concentration, induced prenatally by maternal ethanol intake and in adulthood by chronic ethanol consumption, might mediate changes in stress responsiveness. Animals will be exposed to ethanol either in utero or for varying periods in adulthood, and will be tested to determine 1) pituitary- adrenal response to prolonged or repeated exposure to a stressor; 2) response to chronic unpredictable stress; and 3) recovery following acute or chronic stress. Hippocampal glucocorticoid receptor concentration will be determined in fetal ethanol exposed animals: 1) under basal conditions; 2) following repeated exposure to a stressor; and 3) during recovery from stress. Experiments will also determine whether early handling can attenuate adverse effects of prenatal ethanol exposure on both pituitary-adrenal activity and hippocampal receptor concentration. In adult animals chronically consuming ethanol, hippocampal receptor concentration will be determined at varying intervals following cessation of 3, 6 or 12 weeks of chronic intake. In addition, testing will determine whether subjecting adult "alcoholic" animals to repeated or chronic stress exacerbates ethanol's adverse effect on receptor concentration.